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The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer
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| Zeitschriftentitel: | Endocrinology |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | Endocrinology, 149, 2008, 8, S. 4035-4042 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
The Endocrine Society
|
| Schlagwörter: |
| author_facet |
Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul |
|---|---|
| author |
Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul |
| spellingShingle |
Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul Endocrinology The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer Endocrinology |
| author_sort |
foster, paul a. |
| spelling |
Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul 0013-7227 1945-7170 The Endocrine Society Endocrinology http://dx.doi.org/10.1210/en.2008-0223 <jats:p>The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice.</jats:p> The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer Endocrinology |
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The Endocrine Society, 2008 |
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| title |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_unstemmed |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_full |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_fullStr |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_full_unstemmed |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_short |
The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_sort |
the use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer |
| topic |
Endocrinology |
| url |
http://dx.doi.org/10.1210/en.2008-0223 |
| publishDate |
2008 |
| physical |
4035-4042 |
| description |
<jats:p>The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice.</jats:p> |
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| author | Foster, Paul A., Woo, L. W. Lawrence, Potter, Barry V. L., Reed, Michael J., Purohit, Atul |
| author_facet | Foster, Paul A., Woo, L. W. Lawrence, Potter, Barry V. L., Reed, Michael J., Purohit, Atul, Foster, Paul A., Woo, L. W. Lawrence, Potter, Barry V. L., Reed, Michael J., Purohit, Atul |
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| description | <jats:p>The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice.</jats:p> |
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| spelling | Foster, Paul A. Woo, L. W. Lawrence Potter, Barry V. L. Reed, Michael J. Purohit, Atul 0013-7227 1945-7170 The Endocrine Society Endocrinology http://dx.doi.org/10.1210/en.2008-0223 <jats:p>The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice.</jats:p> The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer Endocrinology |
| spellingShingle | Foster, Paul A., Woo, L. W. Lawrence, Potter, Barry V. L., Reed, Michael J., Purohit, Atul, Endocrinology, The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer, Endocrinology |
| title | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_full | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_fullStr | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_full_unstemmed | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_short | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| title_sort | the use of steroid sulfatase inhibitors as a novel therapeutic strategy against hormone-dependent endometrial cancer |
| title_unstemmed | The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer |
| topic | Endocrinology |
| url | http://dx.doi.org/10.1210/en.2008-0223 |